Rhodium(III)-Catalyzed Oxidative Annulation of Acrylic Acid with Alkynes: An Easy Approach to the Synthesis of α-Pyrones

Article abstract of DOI:10.1002/asia.201801190

A highly efficient rhodium(III)-catalyzed direct oxidative annulation of acrylic acid with alkynes to form α-pyrones was developed. Various substituted acrylic acids were compatible in this transformation, affording the corresponding products in moderate to excellent yields under mild conditions.

Full text of DOI:10.1002/asia.201801190

CHEMISTRY
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Accepted Article
Title: Rhodium(III)-Catalyzed Oxidative Annulation of Acrylic Acid with
Alkynes: An Easy Approach to the Synthesis of α-Pyrones
Authors: Yingting Li, Yan Zhu, Guangliang Tu, Jingyu Zhang, and
Yingsheng Zhao
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10.1002/asia.201801190
Chemistry - An Asian Journal
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Rhodium(III)-Catalyzed Oxidative Annulation of Acrylic Acid with
Alkynes: An Easy Approach to the Synthesis of α-Pyrones
Yu-Ting Li, [a] Yan zhu,[a] Guang-Liang Tu,[a] Jing-Yu Zhang* [b] and Ying-Sheng Zhao*[a]
Abstract: A highly efficient Rhodium(III)-catalyzed direct oxidative
annulation of acrylic acid with alkynes to form the α-pyrone was
developed. Various substituted acrylic acids were compatible in this
transformation, affording the corresponding products in moderate to
excellent yields under mild conditions.
Miura, Ackermann, Jiang, Tanka and Sundararaju through the
oxidative annulation of carboxylic acid and alkynes (Scheme
1)[12]-[16]. These methods provided an atom-economical route to
prepare the α-pyrone and isocoumarin derivatives. For example,
the groundbreaking work was first reported by the group of
Miura through the Rhodium(III)-catalyzed oxidative annulation of
carboxylic acid and alkynes using the copper acetate as the
oxidant (Scheme 1a)[13]. Later, the same group succeeded in
expanding the substrates to the acrylic acid derivatives, when
Introduction
the silver carbonate was used as the oxidant (Scheme 1b)[14]
.
C–H functionalization reactions have provided
a
The group of Ackermann demonstrated that the Ruthenium(II)
complex is an effective catalyst for this oxidative [4+2]
cyclization reaction (Scheme 1c)[15]. In 2014, Jiang and co-
workers disclosed a Palladium-catalyzed oxidative annulation of
acrylic acid with alkynes, where only unsubstituted acrylic acid
was compatible in the transformation (Scheme 1d)[16]. Although
such great results have already been achieved, the substrates
scope of acrylic acids were relatively less explored.
straightforward way to access useful synthetic units in the past
decades, which greatly enriched the route to prepare highly
important compounds in organic synthesis[1]-[6]. The α-pyrone is
a key skeleton in various natural products and bioactive
compounds, such as aurovertin
B
(A), yangonin (B),
desmethoxyyangonin (C) and myxopyronin B (D) (Figure 1)[7]-[9]
.
Scheme 1. The synthesis of α-pyrone derivatives.
Figure 1. Bioactive compounds with α-pyrone skeleton.
Various approaches to the synthesis of these α-pyrone-
based compounds have been well explored[10]-[11]. Considerable
developments have already been achieved by the groups of
Herein we report our recent development of a highly
efficient rhodium(III)-catalyzed oxidative annulation of acrylic
acid with alkynes under mild conditions. Various acrylic acids
were tolerated in this transformation, affording the corresponding
products in good to excellent yields. More impressively, sorbic
acid was also compatible, leading to the corresponding α-
pyrones in good yields.
[a]
Y.-T. Li, Y. Zhu, G.-L. Tu, and Prof. Dr. Y.-S. Zhao
Key Laboratory of Organic Synthesis of Jiangsu Province and
College of Chemistry, Chemical Engineering and Materials Science
Soochow University
Jiangsu, Suzhou 215123, China
E-mail: yszhao@suda.edu.cn
[b]
Dr. J.-Y. Zhang
Results and Discussion
College of Physics, Optoelectronics and Energy & Collaborative
Innovation Center of Suzhou Nano Science and Technology
Soochow University
At the beginning of our study, we firstly treated acrylic acid
1a with diphenylacetylene 2a in the presence of [RhCp*Cl2]2 (1
mol%) and AgOAc (1 equiv) in DCE at 80 C under air for 8 h
Jiangsu, Suzhou 215123, China
E-mail: jyzhang@suda.edu.cn
o
(Table 1). To our delight, the α-pyrone 3a was obtained in 51%
Supporting information for this article is given via a link at the end of
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yield. A series of silver salts including AgOTf, Ag2O, AgF, and
Ag2CO3 were all further tested. The result showed that Ag2CO3
was the best oxidant, leading to the product 3a in 58% yield. We
next explored the effect of solvents such as DMF, 1,4-dioxane,
MeOH, t-Amyl-OH, HFIP and toluene on this transformation.
Gratifyingly, a satisfactory yield of 3a was achieved when HFIP
was used as the solvent. It is worth noting that the reaction
proceeded well with merely 0.5 equiv of Ag2CO3. We next tried
to use other oxidants instead of the silver salts. For example,
groups all provided the corresponding products (3b–3d) in lower
yields. Interestingly, electron withdrawing functional groups have
shown a promoting effect for this transformation, leading to the
corresponding products (3e–3i) in excellent yields. The α-
substituted acrylic acid derivatives were next explored, which all
provided the corresponding products (3j–3l) in good yields. It is
worth mentioning that the presence of free carboxylic acid, furan,
ester and oxethyl were all compatible to this reaction, affording
the corresponding products in good to excellent yields,
highlighting the excellent functional group tolerance of this
method. When the α- and β-substituted acrylic acids were tested,
the corresponding products (3m–3q) were obtained in good to
excellent yields.
when
a
catalytic amount of AgSbF6 (10 mol%) with
Cu(OAc)2▪H2O (0.3 equiv) and K2CO3 (1 equiv) were used
instead of silver carbonate, a dramatical drop in yield of 3a was
observed. The utility of several other oxidants such as
Cu(OAc)2/O2, O2 and benzoquinone were further explored,
however, none of them could afford the product 3a in good
yields. Moreover, the control experiment revealed that the
rhodium catalyst is essential for this reaction (see supporting
information).
Table 2. The scope of acrylic acid derivatives[a], [b]
Table 1. Optimization of reaction conditions[a]
Yield
(%)[b]
Entry
Oxidant
Solvent
1
2
AgOAc (1.0 equiv)
AgOTf (1.0 equiv)
DCE
DCE
DCE
DCE
DCE
DMF
51
N.D.
36
3
Ag2O (1.0 equiv)
4
AgF (1.0 equiv)
34
5
Ag2CO3 (1.0 equiv)
58
6
Ag2CO3 (1.0 equiv)
16
7
Ag2CO3 (1.0 equiv)
1,4-dioxane Trace
MeOH 77
t-Amyl-OH Trace
8
Ag2CO3 (1.0 equiv)
9
Ag2CO3 (1.0 equiv)
10
11
12
13
14
Ag2CO3 (1.0 equiv)
HFIP
toluene
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
95
Trace
95
Ag2CO3 (1.0 equiv)
Ag2CO3 (0.5 equiv)
Ag2CO3 (0.3 equiv)
49
AgSbF6 (10 mol%) + Cu(OAc)2▪H2O (1.0 equiv)
23
15[c] AgSbF6 (10 mol%) + Cu(OAc)2▪H2O (0 .3 equiv)
16[c] AgSbF6 (10 mol%) + benzoquinone (1.0 equiv)
17[c]
18[d]
66
N.D.
38
AgSbF6 (10 mol%)
Ag2CO3 (0.5 equiv)
[a] Reaction conditions: 1b–1q (0.2 mmol), 2a (0.21 mmol), [RhCp*Cl2]2 (1
52
mol%), Ag2CO3 (0.5 equiv), and HFIP (0.2 M). [b] Isolated yields.
[a] Reaction condition: 1a (0.2 mmol), 2a (0.21 mmol), [RhCp*Cl2]2 (1 mol%),
oxidant, solvent (0.2 M). [b] GC yield. [c] K2CO3 (1.0 equiv) was added, In
oxygen atmosphere. [d] Reduced [RhCp*Cl2]2 load to 0.5 mol%, prolonged
time to 24 h.
The scope of the alkynes was further explored under the
optimized reaction condition as illustrated in Table 3. Both hex-
3-yne and oct-4-yne performed well, generating the cyclized
products in excellent yields, respectively. Unsymmetrical
alkylphenylacetylenes could be coupled with acrylic acid,
providing a mixture of substituted pyrones (4c–4e). We next
coupled hex-3-yne with various substituted acrylic acids to
obtain the corresponding α-pyrones in good to excellent yields
(4f–4l).
With optimized reaction conditions in hand, various acrylic
acid derivatives were subjected to the standard reaction to
investigate the functional group tolerance (Table 2). Generally,
the β-substituted acrylic acids all reacted well, affording the
corresponding products (3b–3i) in moderate to good yields. The
acrylic acids substituted with sterically hindered functional
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Table 3. The scope of the alkynes[a], [b]
[a] Reaction conditions: 1r (0.2 mmol), 2 (0.21 mmol), [RhCp*Cl2]2 (1 mol%),
Ag2CO3 (0.5 equiv), and HFIP ( 0.2 M). [b] Isolated yields.
Scheme 3. Reactions of 2-(trifluoromethyl)acrylic acid with alkynes[a], [b]
[a] Reaction conditions: 1s (0.2 mmol), 2 (0.21 mmol), [RhCp*Cl2]2 (1 mol%),
Ag2CO3 (0.5 equiv), and HFIP ( 0.2 M). [b] Isolated yields.
Scheme 4. Gram-scale reactions
[a] Reaction condition: 1 (0.2 mmol), 2b–2f (0.21 mmol), [RhCp*Cl2]2 (1 mol%),
Ag2CO3 (0.5 equiv), and HFIP ( 0.2 M). [b] Isolated yields.
Sorbic acid, used as a food preservative, was firstly
employed in this work as a substrate in the oxidative annulation
of the acrylic acid derivative with alkyne. It was successfully
coupled with diphenylacetylene (2a) under standard reaction
conditions to generate α-pyrone derivative (5a) in good yields.
Interestingly, when unsymmetrical alkynes were coupled with
sorbic acid, only the products 5b–5d were formed without the
generation of any regioisomers (Scheme 2). It is probable that
the steric hindrance effect causes 5b-5d to be the only product.
Trifluoromethyl functional group is highly important in organic
compounds. For the first time, we successfully introduced a
trifluoromethyl group into α-pyrone derivatives using 2-
(trifluoromethyl)acrylic acid as the substrate, highlighting the
synthetic utility of this method (Scheme 3). To further
demonstrate the synthetic significance of this new method,
gram-scale reactions were performed in which 3a, 3f and 3g
were obtained in good yields by prolonging the reaction time to
24 h (Scheme 4).
Based on the previous reports[13]-[14], a plausible catalytic
cycle was proposed for this annulation reaction (Scheme 5). The
carboxyl acid 1a combines with Rhodium(III) catalyst precursor,
followed by an ortho C–H activation, to provide complex I. The
complex I coordinates with alkyne 2a and follows regioselective
migratory insertion to form the key intermediate complex II,
which furnishes the desired product 3a after reductive
elimination.
Scheme 5. Proposed catalytic cycle.
Scheme 2. Reactions of sorbic acid with alkynes[a], [b]
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Conclusions
In conclusion, we have developed an atom-efficient
strategy for the synthesis of α-pyrones via the oxidative
annulation of acrylic acid with alkynes under mild conditions by
employing Rhodium(III) as the catalyst. Various acrylic acids
were tolerated in this transformation, affording the corresponding
products in good to excellent yields. More impressively, the
sorbic acid was also compatible, leading to the corresponding α-
pyrones in good yields.
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Experimental Section
General Procedure for Rhodium(III)-Catalyzed Oxidative
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A mixture of 1 (0.20 mmol, 1.0 equiv), 2 (0.21 mmol, 1.05 equiv),
[RhCp*Cl2]2 (1.2 mg, 1 mol%), Ag2CO3 (27.6 mg, 0.10 mmol, 0.5
equiv) and 1 mL HFIP in a 15 mL glass vial under air
atmosphere was heated at 80 oC with vigorous stirring for 8
hours. The reaction mixture was then cooled to room
temperature, and filtered through celite. The filtrate was
concentrated in vacuo and purified by column chromatography
on silica gel (Ethyl acetate/Petroleum ether = 1:10 to 1:5) to give
the product α-Pyrone derivatives .
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Acknowledgements
We gratefully acknowledge financial support from the Natural
Science Foundation of China (Nos. 21772139 and 21572149).
Project of Scientific and Technologic Infrastructure of Suzhou
(SZS201708) and the PAPD Project are also gratefully
acknowledged.
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Keywords: Rhodium(III)-catalyzed • oxidative annulation •
acrylic acid • α-pyrone • C–H functionalization
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Yu-Ting Li, Yan zhu, Guang-Liang Tu,
Jing-Yu Zhang* and Ying-Sheng Zhao*
Page No. – Page No.
Rhodium(III)-Catalyzed
Oxidative
Annulation of Acrylic Acid with
Alkynes: An Easy Approach to the
Synthesis of α-Pyrones
A highly efficient Rhodium(III)-catalyzed direct oxidative annulation of acrylic acid
with alkynes to form the α-pyrone was developed. Various substituted acrylic acids
were compatible in this transformation, affording the corresponding products in
moderate to excellent yields under mild conditions.
For internal use, please do not delete. Submitted_Manuscript
This article is protected by copyright. All rights reserved.